Opioid-induced neurochemical dysregulation is a critical factor in the exacerbation of mental health disorders and the increased risk of suicide among opioid users. Chronic opioid exposure alters the brain’s neurotransmitter systems, particularly those regulating mood, stress, and cognitive functions, leading to profound neurobiological imbalances. This study examines the mechanisms through which opioid-induced disruptions in dopamine, serotonin, and endogenous opioid pathways contribute to depressive disorders, anxiety, and suicidal ideation. The interplay between opioid-induced hypodopaminergic states, reduced neuroplasticity, and stress-response dysregulation creates a neurochemical environment that heightens vulnerability to self-harm. Additionally, this research explores how opioid use disorder (OUD) interacts with pre-existing mental health conditions, compounding their severity and complicating treatment outcomes. The role of opioid withdrawal in triggering acute psychiatric distress is analyzed, highlighting the link between withdrawal-induced anhedonia, emotional dysregulation, and increased suicide risk. Furthermore, the study evaluates the effectiveness of pharmacological and psychosocial interventions, including medication-assisted treatment (MAT) with buprenorphine and methadone, in mitigating opioid-induced neurochemical disruptions and reducing suicide susceptibility. By synthesizing clinical and neurobiological findings, this study underscores the urgent need for integrated treatment approaches that address both opioid addiction and co-occurring psychiatric disorders. The findings contribute to the broader discourse on mental health and addiction, advocating for targeted interventions that prioritize neurochemical stabilization, harm reduction, and suicide prevention strategies in opioid-affected populations.